Migraine with aura and stroke - the role of warning signs in the context of secondary headaches: case report / Enxaqueca com aura e acidente vascular cerebral ­ o papel dos sinais de alerta no contexto das cefaleias secundárias: relato de caso

Introduction: Headache is a very common complaint in doctors' offices, with primary causes being the majority in relation to secondary ones. Despite this, the identification of secondary headaches is very relevant in clinical practice, since these can be a life-threatening condition, functionality or even a reversible cause. However, imaging screening for all individuals with headache is costly and unrewarding. Therefore, it is important to know the warning signs that, together with the clinical context, lead to a more precise indication of these exams and early and well-targeted therapeutic interventions. Clinical case: This is a 60-year-old man, previously dyslipidemic and smoker, with migraine with aura reported since childhood, who underwent treatment with sodium valproate, with headache attack suppression. About 4 months before admission, he presented with an alteration in the pain pattern, amaurosis fugax in the right eye, dizziness and mild paresis and hypoesthesia in the left side of the body, primarily treated by him as migraine crises, without improvement with the use of triptans. A new outpatient investigation was carried out, which showed multiple small infarcts in the right hemisphere secondary to atheromatous plaque in the right carotid bulb with an obstruction of approximately 85%. Diagnostic and therapeutic arteriography was performed, with stent implantation, uneventfully. Conclusion: The differential diagnosis between migraine with aura and a cerebrovascular event has already been widely reported in the literature and constitutes a pitfall in the routine of headaches, since a serious and potentially disabling condition can be overlooked. The joint evaluation of the alarm signs with the global context becomes an important tool in the propaedeutics of these patients, with knowledge of this casuistry being something relevant within clinical practice.

Introdução: A cefaleia é uma queixa muito comum nos consultórios médicos, sendo as causas primárias majoritárias em relação às secundárias. Apesar disso, a identificação de cefaleias secundárias é muito relevante na prática clínica, uma vez que estas podem ser uma condição potencialmente fatal, funcional ou mesmo uma causa reversível. No entanto, o rastreio imagiológico para todos os indivíduos com cefaleias é dispendioso e pouco recompensador. Portanto, é importante conhecer os sinais de alerta que, juntamente com o contexto clínico, levam a uma indicação mais precisa destes exames e a intervenções terapêuticas precoces e bem direcionadas. Caso clínico: Trata-se de um homem de 60 anos, previamente dislipidémico e fumador, com queixa de enxaqueca com aura desde a infância, que realizou tratamento com valproato de sódio, com supressão das crises de cefaleia. Cerca de 4 meses antes da internação apresentou alteração do padrão álgico, amaurose fugaz em olho direito, tontura e leve paresia e hipoestesia no lado esquerdo do corpo, tratada por ele primariamente como crises de enxaqueca, sem melhora com o uso de triptanos. Foi realizada nova investigação ambulatorial que evidenciou múltiplos pequenos infartos no hemisfério direito secundários a placa de ateroma no bulbo carotídeo direito com obstrução de aproximadamente 85%. Foi realizada arteriografia diagnóstica e terapêutica, com implante de stent, sem intercorrências. Conclusão: O diagnóstico diferencial entre enxaqueca com aura e evento cerebrovascular já foi amplamente relatado na literatura e constitui uma armadilha na rotina das cefaleias, uma vez que uma condição grave e potencialmente incapacitante pode ser negligenciada. A avaliação conjunta dos sinais de alarme com o contexto global torna-se uma ferramenta importante na propedêutica destes pacientes, sendo o conhecimento desta casuística algo relevante dentro da prática clínica.

Associations between migraine and major cardiovascular events in type 2 diabetes mellitus.

BACKGROUND: Migraine is one of the most common primary headache disorders and a well-known risk factor for cardiovascular disorders. We aimed to investigate the association between migraine and major cardiovascular outcomes, including myocardial infarction (MI), ischemic stroke (IS), and cardiovascular death (CVD) in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 2,229,598 people from the nationwide Korean National Health Insurance Service database with type 2 diabetes but without a previous history of MI and IS were included in this study. We identified patients over 20 years of age with migraine using the claim data of International Statistical Classification of Diseases Related Health Problems, Tenth Revision (ICD-10) code G43. The patients with migraine were divided according to their migraine aura status. RESULTS: Migraine was present in 6.3% of the study population. Cases observed for MI, IS, CVD, and all-cause death were 2.6%, 3.6%, 5.9%, and 7.9%, respectively. The diagnosis of migraine was significantly associated with an increased risk of MI, IS, and CVD. The results remained significant after adjusting for covariates, including age, sex, body mass index, alcohol intake, smoking habits, physical activity, economic status, hypertension history, dyslipidemia, and duration of type 2 diabetes (MI, adjusted hazard ratio [aHR]: 1.182, 95% confidence interval [CI]: 1.146-1.219; IS, aHR: 1.111, 95% CI 1.082-1.14; CVD, aHR: 1.143, 95% CI 1.12-1.167). In particular, the presence of aura was associated with a higher risk of MI development compared to the non-aura group. The difference became more prominent with progressing age. CONCLUSIONS: In this nationwide population-based study, people with type 2 diabetes and migraines were found to be at a significantly higher risk for major cardiovascular events, including MI, IS, and CVD. The risk of MI and CVD significantly increased with the presence of aura symptoms among patients with migraine.

Epilepsy in patients with familial hemiplegic migraine.

OBJECTIVE: The coexistence of epilepsy in familial hemiplegic migraine (FHM) has not been reviewed systematically. We investigated the associations of epilepsy in patients with FHM with CACNA1A, ATP1A2, SCN1A or PRRT2 mutations along with clinical and genetic data. MATERIALS AND METHODS: We performed a search in the PubMed bibliographic database and the Cochrane Library was screened for eligible studies, from April 1997 to December 2020. Additionally, Online Mendelian Inheritance in Man (OMIM) was searched for mutations in the CACNA1A, ATP1A2, SCN1A and PRRT2 genes. Brief reports, letters, and original articles about FHM and epilepsy were included in the review if their mutations and clinical course of diseases were identified. RESULTS: Of the included patients with FHM whose information could be accessed, there were 28 families and 195 individuals, 78 of whom had epilepsy; 30 patients had focal epilepsy and 30 patients had generalized epilepsy. All mutations except ATP1A2, which could not be evaluated due to insufficient data, revealed first epilepsy then HM. In 60 patients for whom the epilepsy prognosis was evaluated, only 3.5% of patients were drug-resistant, and the remainder had a self-limited course or responded to anti-epileptic drug treatment. CONCLUSION: Mutations in all three and possibly four FHM genes can cause epilepsy. Contrary to our expectations, the well-known epilepsy gene SCN1A mutations are not the leading cause; the highest number of cases associated with epilepsy belongs to the ATP1A2 mutation. Drug-resistant forms of epilepsy are rare in all FHM mutations, and this information is important for counseling patients.

Association of Migraine With Aura and Other Risk Factors With Incident Cardiovascular Disease in Women.

Importance: Migraine with aura is known to increase the risk of cardiovascular disease (CVD). The absolute contribution of migraine with aura to CVD incidence in relation to other CVD risk factors remains unclear. Objective: To estimate the CVD incidence rate for women with migraine with aura relative to women with other major vascular risk factors. Design, Setting, and Participants: Female health professionals in the US (the Women's Health Study cohort) with lipid measurements and no CVD at baseline (1992-1995) were followed up through December 31, 2018. Exposures: Self-reported migraine with aura compared with migraine without aura or no migraine at baseline. Main Outcomes and Measures: The primary outcome was major CVD (first myocardial infarction, stroke, or CVD death). Generalized modeling procedures were used to calculate multivariable-adjusted incidence rates for major CVD events by risk factor status that included all women in the cohort. Results: The study population included 27 858 women (mean [SD] age at baseline, 54.7 [7.1] years), among whom 1435 (5.2%) had migraine with aura and 26 423 (94.8%) did not (2177 [7.8%] had migraine without aura and 24 246 [87.0%] had no migraine in the year prior to baseline). During a mean follow-up of 22.6 years (629 353 person-years), 1666 major CVD events occurred. The adjusted incidence rate of major CVD per 1000 person-years was 3.36 (95% CI, 2.72-3.99) for women with migraine with aura vs 2.11 (95% CI, 1.98-2.24) for women with migraine without aura or no migraine (P < .001). The incidence rate for women with migraine with aura was significantly higher than the adjusted incidence rate among women with obesity (2.29 [95% CI, 2.02-2.56]), high triglycerides (2.67 [95% CI, 2.38-2.95]), or low high-density lipoprotein cholesterol (2.63 [95% CI, 2.33-2.94]), but was not significantly different from the rates among those with elevated systolic blood pressure (3.78 [95% CI, 2.76-4.81]), high total cholesterol (2.85 [95% CI, 2.38-3.32]), or family history of myocardial infarction (2.71 [95% CI, 2.38-3.05]). Incidence rates among women with diabetes (5.76 [95% CI, 4.68-6.84]) or who currently smoked (4.29 [95% CI, 3.79-4.79]) were significantly higher than those with migraine with aura. The incremental increase in the incidence rate for migraine with aura ranged from 1.01 additional cases per 1000 person-years when added to obesity to 2.57 additional cases per 1000 person-years when added to diabetes. Conclusions and Relevance: In this study of female health professionals aged at least 45 years, women with migraine with aura had a higher adjusted incidence rate of CVD compared with women with migraine without aura or no migraine. The clinical importance of these findings, and whether they are generalizable beyond this study population, require further research.

Early Treatment in Acute Severe Encephalopathy Caused by ATP1A2 Mutation of Familial Hemiplegic Migraine Type 2: Case Report and Literature Review.

Familial hemiplegic migraine type 2 (FHM2) is an autosomal dominant inheritance disorder caused by ATP1A2 mutation, and the clinical spectrum is heterogeneous even with acute severe encephalopathy. However, up to now, early treatments against acute and severe attacks in FHM2 are still insufficient. Here, we report a 15-year-old female with intellectual disability due to FHM2 caused by a pathogenic ATP1A2 gene mutation, presenting mild-to-moderate headache at the onset, followed by confusion, complete right hemiparalysis, epileptic partial seizures, and conscious disturbance with rapid progression in acute attack. Brain magnetic resonance imaging (MRI) and magnetic resonance spectroscopy have revealed left extensive cerebral cortex edema, slightly decreased N-acetylaspartate for neuronal damage, and mildly increased lactate acid for mitochondrial dysfunction throughout the hemispheric swollen cortex. The patient is diagnosed as severe encephalopathy caused by FHM2. Based on literature review about pathophysiologic mechanism described in FHM2 recently, we use early treatments including prevention of glutamatergic excitotoxicity and protection of mitochondria function, as well as traditional antimigraine drug. The symptoms are all greatly improved and recovered within a short time, and follow-up MRI also shows complete disappearance of edema throughout the left hemispheric cortex. Altogether, the approach in our case may reduce the severity and duration of encephalopathy effectively, expend therapeutic options, and provide helpful references for acute severe encephalopathy in FHM2.

Combined hormonal contraception and migraine: are we being too strict?

PURPOSE OF REVIEW: Combined hormonal contraception has been contraindicated in migraines, especially in migraines with aura, because of ischemic stroke risk. Newer formulations are now available and physicians may unnecessarily be limiting access to contraceptive and medical therapeutic options for patients with migraines. This review summarizes the available data regarding ischemic stroke risk of modern combined hormonal contraception in the setting of migraines. RECENT FINDINGS: Limited data exists on current formulations of combined hormonal contraception and outcomes in migraine patients. Studies indicate ischemic stroke risk may be estrogen dose related with high dose formulations having the highest risk. Absolute risk of ischemic stroke with combined hormonal contraception and migraines is low. SUMMARY: Ischemic stroke risk in combined hormonal contraception users in the setting of migraines is low and an individual approach may be more appropriate than current guidelines.

Alien hand syndrome and migraine with aura: A case report.

BACKGROUND: Alien Hand Syndrome (AHS) is an uncontrollable, involuntary, but in appearance, purposeful motor control disorder of the upper extremity. CASE REPORT: A 42-year-old male patient was admitted to our clinic complaining of involuntary motor activity in his right hand. He had a previous history of migraine with visual aura. The uncontrollable motor control disorder was compatible with Alien Hand Syndrome, which was appearing immediately after the visual aura and before the beginning of headache. CONCLUSION: Alien Hand Syndrome is usually observed with anterior cerebral artery infarction, midline tumors, trauma and several neurodegenerative diseases, but is rarely seen in paroxysmal conditions such as migraine with aura.

Migraine and stroke. / Migrene og hjerneslag.

BAKGRUNN: Migrene er en vanlig nevrologisk sykdom som medfører betydelig belastning for den enkelte som rammes, og store helseøkonomiske kostnader for samfunnet. Migrene er forbundet med økt risiko for hjerneslag. Formålet med denne artikkelen er å gi en oversikt over sammenhengen mellom migrene og hjerneslag: både hjerneinfarkt og hjerneblødning, mulige underliggende mekanismer, kliniske implikasjoner og behovet for videre forskning innen feltet. KUNNSKAPSGRUNNLAG: Denne oversikten er basert på litteratursøk i PubMed med definert søkestreng supplert med et pyramidesøk i søkemotoren McMaster PLUS med ordene «migraine¼ og «stroke¼, samt gjennomgang av artiklenes referanselister. RESULTAT: Migrene med aura er assosiert med en dobling av risikoen for hjerneinfarkt, men det er ingen sikker økt risiko blant personer med migrene uten aura. Røyking, p-pillebruk og hyppige migreneanfall øker risikoen. Det ser også ut til å være en noe høyere forekomst av hjerneblødning hos personer med migrene med og uten aura. FORTOLKNING: Sammenhengen mellom migrene og hjerneslag er kompleks. Det er med bakgrunn i økt risiko for hjerneinfarkt ved migrene med aura anbefalt at modifiserbare risikofaktorer som røyking, hypertensjon og p-pillebruk kartlegges grundig og behandles.

Migraine and stroke.

Migraines are generally considered a relatively benign neurological condition. However, research has shown an association between migraines and stroke, and especially between migraine with aura and ischaemic stroke. Patients can also suffer from migrainous infarction, a subset of ischaemic stroke that often occurs in the posterior circulation of younger women. The exact pathogenesis of migrainous infarct is not known, but it is theorised that the duration and local neuronal energy level from cortical spreading depression may be a key factor. Other factors contributing to migrainous infarct may include vascular, inflammatory, endothelial structure, patent foramen ovale, gender, oral contraceptive pill use and smoking. Vasoconstrictors such as the triptan and ergot class are commonly used to treat migraines and may also play a role. Migraine is also shown to be correlated to haemorrhagic stroke, although studies do not demonstrate causation versus association, and further studies are warranted. There are also some rare genetic diseases such as cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy, retinal vasculopathy with cerebral leukodystrophy and others, which can cause both migraines and infarcts. On imaging, many migraineurs are found to have white matter changes similar to those seen in patients with stroke. These may be caused in part by alterations in resting cerebral blood flow and vasoconstrictor use. In treating patients with migraines, it is important to identify and modify any vascular risk factors such as hypertension, smoking, oral contraceptive pill use and lifestyle factors. Further studies will determine if more aggressive treatment of migraines can ultimately lead to fewer strokes in this population.

Migraine and risk of perioperative ischemic stroke and hospital readmission: hospital based registry study.

OBJECTIVE:  To evaluate whether patients with migraine are at increased risk of perioperative ischemic stroke and whether this may lead to an increased hospital readmission rate. DESIGN:  Prospective hospital registry study. SETTING:  Massachusetts General Hospital and two satellite campuses between January 2007 and August 2014. PARTICIPANTS:  124 558 surgical patients (mean age 52.6 years; 54.5% women). MAIN OUTCOME MEASURES:  The primary outcome was perioperative ischemic stroke occurring within 30 days after surgery in patients with and without migraine and migraine aura. The secondary outcome was hospital readmission within 30 days of surgery. Exploratory outcomes included post-discharge stroke and strata of neuroanatomical stroke location. RESULTS:  10 179 (8.2%) patients had any migraine diagnosis, of whom 1278 (12.6%) had migraine with aura and 8901 (87.4%) had migraine without aura. 771 (0.6%) perioperative ischemic strokes occurred within 30 days of surgery. Patients with migraine were at increased risk of perioperative ischemic stroke (adjusted odds ratio 1.75, 95% confidence interval 1.39 to 2.21) compared with patients without migraine. The risk was higher in patients with migraine with aura (adjusted odds ratio 2.61, 1.59 to 4.29) than in those with migraine without aura (1.62, 1.26 to 2.09). The predicted absolute risk is 2.4 (2.1 to 2.8) perioperative ischemic strokes for every 1000 surgical patients. This increases to 4.3 (3.2 to 5.3) for every 1000 patients with any migraine diagnosis, 3.9 (2.9 to 5.0) for migraine without aura, and 6.3 (3.2 to 9.5) for migraine with aura. : Patients with migraine had a higher rate of readmission to hospital within 30 days of discharge (adjusted odds ratio 1.31, 1.22 to 1.41). CONCLUSIONS:  Surgical patients with a history of migraine are at increased risk of perioperative ischemic stroke and have an increased 30 day hospital readmission rate. Migraine should be considered in the risk assessment for perioperative ischemic stroke.

Recurrent coma and fever in familial hemiplegic migraine type 2. A prospective 15-year follow-up of a large family with a novel ATP1A2 mutation.

Background Familial hemiplegic migraine (FHM) is a rare monogenic migraine subtype characterised by attacks associated with transient motor weakness. Clinical information is mainly based on reports of small families with only short follow-up. Here, we document a prospective 15-year follow-up of an extended family with FHM type 2. Patients and methods After diagnosing FHM in a patient with severe attacks associated with coma and fever, we identified eight more family members with FHM and one with possible FHM. All family members were prospectively followed for 15 years. In total 13 clinically affected and 21 clinically non-affected family members were genetically tested and repeatedly investigated. Results A novel p.Arg348Pro ATP1A2 mutation was found in 14 family members: 12 with clinical FHM, one with psychomotor retardation and possible FHM, and one without FHM features. In 9/12 (75%) family members with genetically confirmed FHM, attacks were severe, long-lasting, and often associated with impaired consciousness and fever. Such attacks were frequently misdiagnosed and treated as viral meningitis or stroke. Epilepsy was reported in three family members with FHM and in the one with psychomotor retardation and possible FHM. Ataxia was not observed. Conclusion FHM should be considered in patients with recurrent coma and fever.

[Phenotypic variability in a family with genetically verified familial hemiplegic migraine type 2]. / Fænotypisk variation i en familie med genetisk verificeret familiær hemiplegisk migræne type 2.

After playing handball, a 13-year-old girl developed a comatose condition during 7-10 days with hemiparesis and aphasia. From age three to nine she was treated for partial epilepsy. She never had symptoms of migraine. Her father had childhood epilepsy and at the age of 40 and 44 he experienced two attacks with prolonged coma, fever, seizures, hemiparesis and aphasia. His mother had symptoms of severe hemiplegic migraine. Father and daughter were genetically tested and an earlier described mutation in ATP1A2 gene was found. These cases illustrate the phenotypic variability in familial hemiplegic migraine type 2.

Migraine with aura is associated with impaired colour vision: Results from the cross-sectional German DMKG headache study.

BACKGROUND: Hypersensitivity to light, noise and odour are pivotal clinical characteristics of migraine associated with enhanced cortical excitability and dysfunctional habituation. However, little is known about the integrity of basic sensory functioning in migraine on a population-based level. METHODS: A total of 129 participants with migraine (105 without aura, MwoA, 24 with aura, MA) and 522 healthy controls without headache 12 months prior to baseline were included from a sample of the DMKG study and underwent standardised clinical sensory testing of smell, taste, hearing and vision. RESULTS: After adjustment for age, sex, smoking status and history of head injuries, the chance of impaired colour perception was significantly higher in MA compared to controls (odds ratio, OR=3.20; 95% CI=1.20-8.53) and MwoA (OR=3.62; 95% CI=1.31-9.97). Compared to MwoA, MA also had an increased chance of smell (OR=3.20; 95% CI=0.98-10.42) and taste (OR=2.58; 95% CI=0.90-7.40) impairment. CONCLUSIONS: In this cross-sectional, population-based study on sensory functioning in migraine participants, colour vision was impaired interictally in MA compared to MwoA and controls.

Insulin resistance in migraineurs: results from a case-control study.

OBJECTIVES: Several studies have suggested an association between migraine and insulin resistance (IR) without adequately addressing the issue according to migraine type. We assessed IR in subjects with migraine with aura (MwA) and migraine without aura (MwoA) to estimate the consistency of the possible association. METHODS: In a case-control study we included case subjects with MwA and MwoA, who were consecutively selected from those referred to our Regional Headache Center from September 2011 to February 2013, and age-matched control subjects selected using general practitioners' databases. IR was calculated by means of the homeostatic model assessment of IR (HOMA-IR), ß-cell function (HOMA-B), and the quantitative insulin sensitivity check index (QUICKI) measuring glucose and insulin values in a blood sample collected in the morning after overnight fasting. Data regarding anthropometric measures, comorbidity risk factors, and migraine characteristics were also recorded. RESULTS: We recruited 50 case subjects with MwA (38 women) and 50 with MwoA (40 women) and 50 control subjects (40 women). Proportions of arterial hypertension, cigarette smoking, hypercholesterolemia, use of oral contraceptives, and mean values of the body mass index (BMI) were similar in the three groups. We found significantly different glucose values among and within groups considering case subjects with MwA and MwoA and control subjects (4.9 ± 0.6 vs 4.7 ± 0.5 vs 4.6 ± 0.5 mmol/l; P = 0.018) in the absence of any difference in insulin (53.1 ± 24.0 vs 56.7 ± 34.4 vs 53.8 ± 24.4 pmol/l; P = 0.811), HOMA-IR (1.6 ± 0.8 vs 1.7 ± 1.0 vs 1.6 ± 0.7; P = 0.765), HOMA-B (121.4 ± 71.1 vs 149.2 ± 93.8 vs 162.8 ± 109.7; P = 0.107), and QUICKI (0.36 ± 0.03 vs 0.37 ± 0.03 vs 0.37 ± 0.03; P = 0.877) values. The logistic regression model showed increased odds of MwA in subjects exposed to the highest tertile of glucose values. This association was confirmed in the adjusted model, in which case subjects with MwA were compared with those with MwoA but not with control subjects. CONCLUSIONS: In contrast to what has been shown by the majority of the available studies, the results of our study do not support the association of migraine with IR. As our study was not population-based and several patients had low disease activity, these findings need further confirmation.

Unrecognized paraganglioma of the urinary bladder as a cause for basilar-type migraine.

Extra-adrenal paraganglioma with isolated localization in the urinary bladder is a rare neuroendocrine tumor. Although the typical symptoms like headache, nausea, weight loss, flushing, heart palpitation or paroxysmal hypertension during micturition are well established, we present an unusual case of bladder paraganglioma, 'misdiagnosed' with basilar-type migraine due to headache for the past 8 years. As urologists linked the presence of a tumor (by CT) and symptoms connected with micturition, no cystoscopy and no transurethral resection of the bladder was performed prior to detailed diagnostic workup. After diagnosis of an extra-adrenal paraganglioma, the patient was scheduled for open partial cystectomy. In consideration of the fact that bladder paraganglioma is an infrequent genitourinary cancer, this case report clearly points out the importance of an exact anamnesis and clinical examination to minimize the probability of misdiagnosis with possible fatal consequences in any case with clinical suspicion of bladder paraganglioma.

Functional characterization of a novel C-terminal ATP1A2 mutation causing hemiplegic migraine and epilepsy.

BACKGROUND: We describe a four-generation Italian family with familial hemiplegic migraine (FHM) and epilepsy due to a novel ATP1A2 missense mutation (R1007W). CASE RESULTS: Mutational analysis revealed a heterozygous nucleotide substitution c.3019C>T resulting in the missense substitution p.Arg1007Trp (p.R1007W) in seven subjects: Three individuals had hemiplegic migraine, two exhibited a clinical overlap between migraine and epilepsy, one had migraine and one was unaffected. The identified ATP1A2 mutation was not found in an ethnically matched control population of 190 individuals and was not reported in a polymorphisms database. In two-electrode voltage-clamp experiments on XENOPUS oocytes, the ATP1A2 R1007W mutant showed (i) reduced ion pumping activity due to a more profound voltage dependence and (ii) decreased apparent affinity for extracellular K⁺ at voltages around the cellular resting potential. This distinct type of loss of function has not been reported for other FHM2 mutations and can lead to impaired K⁺ clearance and elevated K⁺ levels in the CNS. CONCLUSIONS: The functional data and clinical evidence suggest that in FHM2 migraine and epilepsy may originate from the same pathogenic mechanisms associated with genetically determined alterations of ion channels and pumps. Our data also support the hypothesis that the new mutation R1007W in our family may be a susceptibility factor for epilepsy.